Involuted endovascular valve and method of construction

ABSTRACT

A prosthetic tri-leaflet valve formed by involuting a portion of a tubular structure inside itself. The valve can be made by a method comprising providing a tubular segment in which three equidistant longitudinal incisions are made in one end of the tube creating three flaps which are involuted, i.e., folded, in toward the inside of the tube and the edges of the flaps secured to the inner wall of the tube to form leaflets. The tube can be formed of a single sheet of synthetic, organic or biological material and can be solid, woven, braided or the like. A braided configuration permits the valve to be annularly compressed and delivered to the site using a minimally invasive delivery mechanism, then expanded at the implantation site.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a national phase application of, and claims priorityfrom, International Application No. PCT/US03/14160, filed May 5, 2003,under 35 U.S.C. 371, which claims the benefit of priority from U.S.Provisional Patent Application No. 60/377,721, filed on May 3, 2002. Theentire contents of both applications are incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates to a prosthetic valve with an involutedstructure. The present invention also relates to methods and apparatusfor constructing an involution valve.

BACKGROUND OF THE INVENTION

Since the implant of the first cardiac valvular prosthesis in theanatomic position in 1960, more than 50 different cardiac valves havebeen introduced over the last forty years. Unfortunately, after years ofdevelopment of mechanical and tissue valves there remain significantproblems associated with both types of valves.

Mechanical vs. Tissue Valves

Mechanical valves are durable in patients but require long-termanticoagulation therapy. Tissue valves offer freedom fromanticoagulation therapy and the problems of bleeding, but tend todegenerate rapidly, particularly in younger patients. The most commonlyimplanted tissue valves are constructed from chemically-treated animaltissues (i.e., glutaraldehyde-fixed pericardial or porcine valves). Thepreservation, sterilization, and fixation processes currently used intissue valve preparation are believed to contribute to the lack oflongevity of tissue valves.

Ross Procedure

One alternative approach for aortic valve replacement has been totranspose the patient's own pulmonary valve into the aortic position inthe same individual, as described by Ross in the late 1960's. Although atechnically demanding procedure, the Ross procedure frees the patientfrom anticoagulation therapy and has substantial longevity compared toother types of tissue valves. A disadvantage of using the pulmonaryvalve to replace the aortic valve in the same patient is that thepulmonary valve must also be replaced. Most commonly, the replacementtissue for the excised pulmonary valve is a valve (aortic or pulmonic)derived from a cadaver (“homograft”). Problems arise from lack of donoravailability and size mismatches between the donor homograft and theliving recipient. Unfortunately, replacing the pulmonary valve with ahomograft is associated with immunologically-mediated stenosis in somepatients which limits their longevity.

Monocusp Procedure

Alternatively, a single flap of tissue from the pulmonary trunk has beenused to create a pulmonary “mono-cusp” valve in pediatric patientsundergoing the Ross procedure. Long-term function of the monocusp valvehas yet to be documented. Historically, it is known that a singleleaflet valve design has a less efficient closure than a tri-leafletvalve. The suboptimal function of a monocusp valve may adversely impactlong-term results. It is a drawback that the mono-cusp procedure isrestricted to replace a valve at the location where the tissue flap iscreated. The monocusp procedure does not provide a source forreplacement of valves other than the pulmonary valve.

Trileaflet Valve Derived from Pulmonary Artery Tissue

Another previously described method to replace the aortic valve entailssurgical reconstruction of a tube of tissue from the pulmonary artery ofthe same individual. In this procedure, a tube of tissue was harvestedfrom the pulmonary trunk and reconfigured into a trileaflet valve. Inorder to create a valve, the base of the pulmonary tissue tube wassutured to the aortic annulus and to the aortic wall at three points.This procedure was attempted in three pediatric patients and abandoneddue to immediate and severe aortic insufficiency in two patients. Thefailure of this valve replacement procedure resulted, in part, from theextreme technical challenge for the surgeon. In this procedure, thesurgeon must simultaneously construct and implant the valve whileattempting to surgically compensate for any size discrepancies betweenthe donor tissue and the recipient valve site.

As described previously, promising attempts to create a tissue valve byreconfiguring an individual's own living tissues have been problematic.It would be advantageous to have a method to more efficiently,effectively, and reliably construct a functional and durable tissuevalve. It would be desirable for the valve to be a non-immunogenicstructure capable of cellular regeneration and repair.

U.S. Pat. No. 5,713,950, issued to Cox discloses a valve constructedfrom a tubular structure. This invention is a nesting of tubes dependenton multiple suture lines or points to join the tubes to create avalvular structure. It is a drawback that these sutures are positionedin areas of high stress during the function of the valve through thecardiac cycle. Although this valve is a simple design, it would beinefficient and difficult to use this method to reconfigure thepatient's own tissues into a valvular structure.

U.S. Pat. No. 6,494,909, issued to Greenhalgh, discloses a device andmeans for a braided valve and minimally invasive deployment. Theinvention does not describe the area of attachment of the leaflets tothe walls of the tubular structure to create a functionalthree-dimensional tri-leaflet valve. This invention does not describe ameans for creating an autologous or living tissue valve. It is a furtherdisadvantage that this invention describes that it is placed in acatheter for deployment. This is distinguished from other braidedstructures which are deployed by an internal mechanism with thepotential for more maneuverable and narrower insertion profiles (such asthat disclosed in Patent Cooperation Treaty application (designating theU.S.) No. PCT/US02/40349, filed Dec. 16, 2002, entitled “DYNAMICCANNULA,” and commonly assigned to the assignee of the presentinvention, the disclosure of which application is incorporated herein byreference in its entirety).

SUMMARY OF THE INVENTION

In one exemplary embodiment, the present invention provides forconstructing a prosthetic valve by a technique referred tointerchangeably as the “involuted cylinder” or “involution” method. Theinvolution valve may be constructed of synthetic, semi-synthetic,organic or biological material or mixtures or combinations thereof. Thevalve is efficient to construct, may be derived from the patient's owntissues, and is particularly suitable for replacement of aortic orpulmonic valves.

In one exemplary embodiment, the present invention provides a valveconstructed of a tubular structure involuted inside itself. Thethree-dimensional shape of the “involution valve” may be provided byfolding, braiding, weaving, knitting, or combinations of theseoperations on the material. The material may be biological, synthetic,semi-synthetic, organic, or a combination of these materials. Thepatient's own tissue (e.g., pericardium, pulmonary artery, or aortictissue) can be reconfigured into a functional valve using this method.Some examples of material sources include, but are not limited to,tissue derived from the same individual (e.g., pericardium, aortic, orpulmonary artery tissue) or a different individual of the same species(e.g., cadaver tissue) or a different species (e.g., decellularizedporcine small intestinal submucosa).

The valve may be a scaffold, matrix, or other structure that undergoes amaturation process of living autologous cell deposition thereon. For thepurposes of the present disclosure, the term scaffold will be referredto in an exemplary, but nonexclusive, manner. An example of apotentially suitable scaffold substance is decellularized porcine smallintestinal submucosa. The scaffold could provide signaling to cells toorganize as an autologous valve, provide a support structure for cellorganization, or function as a non-immunogenic valve regardless of cellpopulation. The scaffold can be a permanent, semi-permanent, ortemporary structure capable of resorption or remodeling. In this manner,the valve would, when implanted and the patient adapted, have a lack ofexposed immunogenic material.

The present invention provides a method of forming a valve or valvescaffold, comprising, in one exemplary embodiment: (1) providing a tubeof material, (2) involuting the tube inside itself, (3) selectivelyattaching portions of the inside tube to the outer tube of material, (4)implanting the valve in a patient.

Accordingly, it is a feature of the present invention to provide a valvethat has minimal immunogenic structure.

It is another feature of the present invention to provide a valve thatis capable of cellular regeneration and repair and that is functionaland durable.

Other features and advantages of the present invention will becomeapparent upon reading the following detailed description of embodimentsof the invention, when taken in conjunction with the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The various features and advantages of the invention will be apparentfrom the attached drawings, in which like reference characters designatethe same or similar parts throughout the figures, and in which:

FIG. 1 shows a cutaway view showing an exemplary embodiment of aninvolution valve of the present invention implanted in the aortic valveposition on the left (systemic) side of the heart;

FIG. 2 is a cutaway view showing the involution valve implanted as apulmonic valve replacement on the right (pulmonic) side of the heart;

FIG. 3 shows material in a braided configuration;

FIG. 4 shows material in knitted configuration;

FIG. 5 shows material in a woven configuration;

FIG. 6 shows material in a triaxial weave;

FIG. 7 shows a perspective view of multi-directional layering ofmaterials;

FIG. 8 shows material in a full Leno weave;

FIG. 9 shows a perspective view showing a cylinder formed from a sheet;

FIG. 10 shows a perspective view of a collapsible braided cylinder;

FIG. 11 shows a perspective view of a cylinder with three equidistantincisions to create flaps or “leaflets”;

FIG. 12 shows a perspective view of involution of the flaps inside thecylinder to create leaflets;

FIG. 13 shows a perspective view of an exemplary embodiment of aninvolution valve showing attachment of the leaflets to the inner side ofthe outermost tube with “U” sutures;

FIG. 14 shows a perspective view of the involution valve depictingscalloping of the outermost wall to allow for subcoronary implantationand preservation of the Sinuses of Valsalva;

FIG. 15 shows a perspective view of an exemplary embodiment of aninvolution valve constructed by involuting the tube inside itselfwithout incisions to create flaps;

FIG. 16 shows a perspective view of a braided cylinder involuted insideitself to form an inner tube with a reduced diameter that acts as aone-way valve that opens under pressure;

FIG. 17 shows a perspective view of an involution valve constructed witha cuff of material at either end;

FIG. 18 shows material in a looped or tufted configuration;

FIG. 19 shows a finite element analysis of the involution valvedepicting an area of high stress at the attachment area of the inner andouter walls of the valve, with a gray scale such that high stress areasare shown in black and low stress are shown in white;

FIG. 20 shows a perspective view of the involution valve showing theattachment of the inner and outer tube by weaving them together in aninterleaflet triangular pattern;

FIG. 21 shows a perspective view of the involution valve showing sinusesenlarged by providing excess material between the annulus and thesinotubular junction with the creation of interleaflet triangle byselectively weaving the inner tube to the outer tube between sinuses;

FIG. 22 shows a top view of the involution valve depicting excessleaflet material in the radial and circumferential directions.

FIG. 23 shows a perspective view of the involution valve depictingexcess leaflet material in the longitudinal plane;

FIG. 24 shows a perspective view of the involution valve depicting theintegration of a rigid or semi-rigid stent into the structure;

FIG. 25 shows a perspective view of the involution valve depicting theouter with cut away sections for coronary artery reimplantation intendedfor use with “inclusion” or “mini-root” valve implantation techniques;and,

FIG. 26 shows a perspective view of the involution valve as collapsiblebraid depicting the ability of the structure to assume a reversiblenarrow endovascular insertion profile.

DESCRIPTION OF THE INVENTION

The present invention generally provides a prosthetic valve formed byinvoluting a tubular structure inside itself The present invention alsoprovides methods of forming an involution valve.

Primary Structure: Synthetic, Organic, and Biological Materials

In one exemplary embodiment of the present invention an involution valveis formed of synthetic or processed organic material. The material canbe any of a number of different biologically inert materials. Thefollowing materials are set forth by way of illustration only and arenot intended to be exclusive.

Synthetic Materials

Polyglycolic acids (PGA) can be used as non-woven mesh, having highporosity, good cell attachment, good growth and extracellular matrixformation, rapid bioabsorption, and biocompatibility. Examples ofmaterials include, but are not limited to, polyhydroxyalkanotes (PHA orPHO); poly-4-hydroxybutyrates (P4HB) (PHA and P4HB have the propertiesof elasticity, mechanical strength, thermoplasticity, and havedemonstrated increase in cell attachment during seeding with increasedcollagen development); PGA and P4HB hybrid in the form of thin PGAcoated with P4HB to reduce stiffness but provide mechanical strength;absorbable and nonabsorbable suture materials, polylactic acid (PLLA);polycaprolactone; fibrin-gels (moldable); hydrogels (polyethyleneglycol-based hydrophilic substances); dacrons; metals, or nitinolsparticularly biodegradable nitinols); mixtures and/or combinationsthereof and the like.

Organic Materials

The valve may also be constructed of polymer-based substances; examplesinclude, but are not limited to, polypropylene, polyester, silk, nylon,plastics, rubbers, silicones, papers or other suitable cellulose basedproduct, polytetrafluoroethylenes (PTFE's), polyurethanes, mixturesand/or combinations thereof and the like.

Biological Materials

Pericardial tissue, arteries, veins, portions of the gastrointestinaltract, combinations of the forgoing and the like can be used. Thematerial can be a chemically-treated tissue such as glutaraldehyde-fixedpericardium or other suitable tissue.

Tissue can be harvested, isolated (for example, a segment of tubularblood vessels such as the autologous pulmonary artery trunk, left orright pulmonary artery, and aorta), created (cell cultures) or tissueengineered (for example, cells populating a scaffold). The livingmaterial can continuously bathed in, for example, cell culture medium orHank's solution so as to retain viability. Tissue sources includeautologous (self) tissues, xenograft (e.g., decellularized animaltissues) or allografts (e.g., cadaver tissue). More specific examples ofthese include decellularized porcine small intestine submucosa (“SIS”)and segments of a decellularized aorta, or vena cava tissue from cadaverdonors. An example of a decellularization process is incubation of intrypsin/EDTA for 48 hrs to extract endothelial cells and myofibroblasts.

In one exemplary embodiment, the scaffold is decellularized porcinesmall intestinal submucosa which is reconfigured into a valvularstructure, implanted into the individual, and allowed to mature bypopulating with autologous cells. Population of the scaffold withautologous cells can occur outside (e.g., in pulsatile cell culture“bioreactor”) or inside the body (e.g., following implantation).Exposing the cell-populated scaffold to mechanical stresses has beenshown to physically signal the cells to produce extracellular matrixmaterial. The mechanical stresses may influence the mass,directionality, strength, and types of biomolecules (e.g., collagen) andcells integrating with the scaffold.

The materials described previously, as well as others, may be used tocreate a functional three-dimensional valve or scaffold using a methodof the present invention. The valve is then implanted into the body, anddepending upon the material and the configuration, allowed to mature byhealing, endothelialization, autologous cell seeding, and extracellularmatrix deposition

Secondary Structure: Homogeneous, Non-Homogenous, and Porosity, andLayering

Homogeneous

The texture or surface structure of the valve material is significantand may be homogeneous or non-homogeneous. Human heart valves and theentire human endovascular system is lined with a smooth homogeneouslayer of endothelial cells which serve a multitude of functions,including the prevention of thrombus formation. The material for thepresent invention may be living tissue such as blood vessels from thepatient. In this case, the valve's surface is lined, in part, with ahomogeneous layer of endothelial cells.

Other parts of the involution valve, such as an adventitial layer, whichare exposed to the endovascular space, may pose a risk to form thrombus.In time following implantation, the non-endothelialized surfaces havethe potential to be populated with a homogeneous layer of endothelialcells In most instances, it is preferable for the valve to besubstantially completely lined with a smooth homogenous layer ofendothelial cells on all surfaces that contact blood. Temporary systemicanticoagulation therapy in this patient during the endothelizationperiod may reduce or eliminate the risk of thrombus formation.Alternatively, chemicals, drugs, growth factors and other agents thatpromote endothelization and retard thrombus formation may be bound tothe valve material to provide local therapy.

In another case, the starting material for valve construction ispericardial tissue which has a smooth side (faces the heart's surface)and a rougher side of collagen and other constituents. Despite thehomogenous nature of each side of these materials (e.g., human bloodvessels or pericardium), the involution valve may be preferentiallyconstructed such that the smooth side is the diastolic surface and therough side faces the systolic side of the blood flow during the cardiaccycle. It appears to be advantageous to have the valve involuted suchthat the most homogeneous, smooth, endothelialized surface is facing thediastolic side of the circulation. This follows from the previousobservations of others that tissue valve material undergoes degenerativechanges and tends to form thrombus on the diastolic side versus thesystolic side of the leaflets. The anatomical orientation in thecirculation of the present invention as an aortic valve replacement isdepicted in FIG. 1 and is described further in Example 1. A pulmonicvalve substitution with the involution valve is shown in FIG. 2 anddescribed in more detail in Example 2. The involution valve may also besuited in other anatomical positions such as for replacement of a mitralor tricuspid valve. The present invention may also serve as a treatmentfor aortic insufficiency with implantation of the involution valve inthe descending aorta.

Non-homogeneous

The material of the involution valve may also be non-homogeneous. Forexample, the material can be provided as a laminate, mesh, knit, wovenor nonwoven material, braids, strands, combinations thereof and thelike. Meshes, braids (FIG. 3) knits (FIG. 4), and weaves (FIG. 5) can beformed from interlocking, interlacing, or interweaving connecting fibersof scaffold materials. (e.g., strands of arteries, veins, or otherautologous tissues woven, knitted, or braided into a sheet or cylinder);

These materials and fabrication methods may be exploited for theirphysical characteristics. For example, rib knit may be useful given itsproperty of elasticity in its width direction. Jersey knit is known tohave good wrinkle recovery and excellent drape. Double knits are knownto be strong since production of the material is carried out on acircular-knitting machine with two sets of perpendicular needles. Thephysical characteristics of these materials and fabrication techniquesmay be exploited in light of the anatomy of the native human valve toconstruct a valve replacement with desirable elasticity, wrinkles, andstrength properties.

Consider that the histology of the human native semilunar valves isreferred to as highly anisotropic (i.e. not the same in all directions).It follows that the biomechanics of the “cusps” or “leaflets” are notthe same in each direction. The leaflets are known to have grosswrinkles or “corrugations” of collagen fibers which expand perpendicularto the cuspal free margin (i.e. radial direction) and imparts a highcompliance on the leaflet in this direction. The less compliant “crimp”or “pleat” in the collagen in circumferential direction is a predominateload bearing element, restricting leaflet during filling and cuspdistention Strength is provided by groups of collagen cords radiate fromthe commissures (attachment points of leaflets to wall). Thesestructural features enable the cusps to be pliable when the cusps areunloaded and the heart is contracted (systole), but inextensible when aload is applied during cardiac filling (diasole).

It may be advantageous to impart the physical properties of the humannative valve to the present invention. For instance, one couldpurposefully choose a rib knit or jersey knit configuration of thematerial along the radial or circumferential direction of the valveconstruct in order to impart elasticity or draping characteristics tothe leaflets. Imparting compliance to the valve leaflet has thepotential to dissipate the force imposed by the cardiac cycle on thevalve. This may increase strength and durability to the valve followingimplantation.

In prior studies of others, tissue engineered valve scaffolds haveselectively populated with extracellular matrix material when stresses,such as imposed by the cardiac cycle, were mimicked in vitro. Asexemplified, the selective use of the materials and fabricationtechniques may be used to control the compliance and strength of thevalve of the present invention. Controlling the physical properties ofthe materials and fabrication methods in this manner has the potentialto more accurately signal the extracellular matrix materials and thecells that produce them to populate according to conditions that moreprecisely model the native system.

Strands or fibers of material may be elastic or nonelastic. The fiberdiameter can vary in the same or in different fibers composing thematerial. One study using polyglycolic acid as a scaffold material invalve construction, advocated a fiber diameter of 12-15 μm. In certaincases, fiber diameter can be custom-extruded. The fiber may berectangular, round, or twisted around itself in a clockwise orcounterclockwise position. Each fiber could be a bundle of smallerdiameter fibers.

Pores

Porosity of the scaffold material may be significant. The pores orspaces in the material may purposefully be sized to retard thrombusformation and promote endothelization and adhesion of circulatingautologous cells. The scaffold materials themselves may be rough orsmooth and the pores between them can form smooth shapes or shapes withsharp angles. Variables include pore shape, pore size, open or closedqualities, interpore connectivity, and pore wall morphology. Pores canbe the spaces in a weave, braids, or knits. Pores can be introduced intothe material by a variety of different techniques, including, but notlimited to, cell opening agents and mechanical aperturing. The pores orspaces in the material may purposefully be sized to retard thrombusformation and promote endothelization and adhesion of circulatingautologous cells.

In another instance, materials used to construct the valve could changetheir homogeneous properties and pore size. For example, if oneconstructed a weave of strands of decellularized porcine small intestalsubmucosa material, the hydrophilic nature of the material is such thatit may form smaller pores and a more homogeneous structure afterhydration or implantation in the body.

In certain substances, complex pore geometry (e.g., honeycomb shapedpores) can be created by dispersing paraffin spheres in the dissolvedscaffold material (e.g., PLLA and PGA). The paraffin is subsequentlydissolved to create pores in the scaffold material. Another technique isto use salt-leaching/sugar crystals/glass crystals to yield a porousmatrix. The size of the pores can homogeneous (PGA) or heterogeneous(PLA). The scaffold pore sizes can range from approximately 100-500microns, more preferably in the 100 to 240 micron range. Otherinvestigators using PLA and PGA scaffolding have noted a decrease incompressive modulus for smaller pore sizes (100-200 microns) as comparedto large pore sizes (250-350 or 420-500 microns).

The pores in the material or the orientation of spaces between thematerials can be purposefully used to impart strength or elasticity tothe valve. For example, a triaxial weave is a process of weaving threestrands of material at 60 degree angles to one another (FIG. 6). Theresulting material has limited or no stretch or distortion in anydirection. If equal size and number of strands are used in all threedirections, the final material approaches equal strength and stiffnessin all directions.

Layering

The valve materials can be single or multi-layered. The layers can beorientated such that the directionality of the materials is parallel,perpendicular, or angled. For example, the material may be “biased”,“radial”, or a combination (“biased/belted”) such as that used inautomobile tire construction. In a bias construction the material islaid alternating at bias angles of 25 to 40 degrees to the surface layerdirection. In a radial design a layer is 90 degrees to the surfacematerial direction. Between these layers can be a series of alternatinglayers at low angles of 10 to 30 degrees to the surface direction. Acombination of these may also be used. The directionality within eachlayer and orientation of the layers in respect to one another may beused to selectively impose strength and elasticity to the valve (FIG.7).

It is known from prior anatomical studies that the human semilunar valveleaflet consists of three histologically distinct layers; theventricularis, the spongiosa, and the fibrosa. The ventricularis facesthe inflow surface and consists of mostly collagen “corrugations” withradially aligned elastic fibers. The spongiosa is composed of looselyarranged collagen and glycoaminoglycans. The fibrosa opposes the outflowsurface is mainly circumferentially arranged, “crimped,” densely packedcollagen fibers, mostly parallel to the free edge of the leaflet. Withthis in mind, the present invention could be constructed of layeringmaterial purposefully arranged. For example, the top layer (the futureinflow surface of valve leaflet) may be compliant in the radialdirection and the most bottom layer could have a directionalityperpendicular to the top layer, imparting less compliance in thecircumferential direction. A middle layer could be sandwiched in betweenwhich has an multi-directional, oblique, or loosely arranged material.

Investigators have expressed concern that the use of layering, and inparticular, lamination of porcine small intestinal submucosa, maydelaminate inappropriately following implantation. One way to overcomethis would be to weave, knit, or braid the material to preventdelamination. A specific example is the use of a Leno weave in which thestrands are arranged in pairs with one twisted around the other betweenother strands (FIG. 8). This weave imparts firmness and strength to thematerial and prevents slippage and displacement of the strands.Alternatively, in certain instances, layering could be avoided byweaving, knitting, or braiding from a single layered strand.

Tertiay Structure: Tubes, Sheets, and Sleeves

The scaffold can be formed according to the following exemplary method.A quantity of material is provided as a tube or as a sheet. If it isprovided as a sheet, two opposing sides are joined together to form atube by any of a number of techniques known to those skilled in the artand appropriate to the material being used, such as, but not limited to,weaving, interlacing, braiding, knitting, punching, tufting, laminating,suturing, stapling, gluing, welding, fusing, combinations thereof andthe like (FIG. 9). The sheet can be knitted, woven, or braided fromstrands of material. A tubular or cylindrical structure can be createdby sleeving techniques using braiding, knitting, weaving or combinationof these methods. The structure can be a proper cylinder (the termcylinder and tube being used interchangeably in the present disclosure)or a slightly conical segment. The thickness of the scaffold cylindercan range from about 0.3 mm to 1.0 mm, although it may be thinner orthicker.

One advantage of a tubular braid configuration is the possibility ofcreating a tubular valve that is collapsible (FIG. 10). Braided tubescan be constructed which reduce diameter significantly when alongitudinal force is exerted on the tube. In one instance the diameterof the tubular valve can be reduced in diameter, introduced into theendovascular space in minimally invasive manner, and deployed into alarger diameter structure at the valve replacement site (seeImplantation section herein).

Quaternary Structure: Involution, Attachment, Interleaflet Triangles,Sinuses, Leaflet Modifications, and Stents

Involution

Creating leaflets by involution allows the material at the site of theinfolding (i.e., the base of the valve) to retain its compliant nature.This may improve valve durability by facilitating the transfer ofstresses and strains on the leaflets to the wall of the implant site(e.g., aortic root). Since the valve is created prior to insertion, itcan be tested prior to use and the valve function is not whollydependent on surgical implantation techniques.

In one geometry of the involution valve shown in FIG. 11, the height “h”of the cylinder 12 is approximately equal to the diameter “d” of thevalve implantation site (annulus diameter). Approximately half of thecylinder wall height form the leaflets which span half the diameter ofthe annulus. The remaining half of the cylinder wall forms the height ofthe commissures. The height of the commissures is based on theanatomical relationship of annulus to sinotubular junction distanceverses annulus diameter in same patient, i.e., height of commissures isapproximately half the annulus diameter. The material has a thickness“t”.

In one exemplary embodiment, three longitudinal incisions about 120degrees apart are made in the cylinder to create three flaps of tissue.Preferably, though not mandatorily, the length “L” of the incision isapproximately one half the height of the tissue cylinder height “h” lessabout twice the tissue thickness “t”; i.e., L=½h−2t. The length “L” ofthe incision should preferably be less than half the height “h” of thecylinder in order to eliminate a potential hole in the base of the valvecaused by the incisions.

As shown in FIG. 12 the cylinder is involuted into itself such that theinnermost wall (in this case, the three flaps) become the “leaflets” ofthe valve and the outermost wall becomes the site of attachment to theimplantation site. The leaflets are secured to the inner side of theoutermost wall (FIG. 13). If the valve construct is intended to beimplanted in the aortic valve position, the outermost wall of the valveconstruct may be scalloped to allow for subcoronary implantation (FIG.14).

In particular, with tubes of tissue such pulmonary artery, thelongitudinal incisions in the cylinder release the constraints on thematerial and allow the flaps to be easily involuted and secured to theinner wall of the cylinder. Although, the incisions are not necessary,they allow each flap to be secured to the wall independently and mayhelp the leaflets move distinctly from one another during the cardiaccycle. In addition, the perpendicular attachment of each leaflet edge tothe wall may facilitate proper tissue repair and growth at eachcommissure. The presence of incisions at the commissure sites maypromote healing and collagen deposition at the commissures.

In another embodiment, no incisions are made and the tubular structureis simply involuted inside itself and selectively attached to theoutermost wall (FIG. 15).

In another embodiment, a braided tube is involuted inside itself and theinner tube forms a passively closed inner tube structure or one-wayvalve in part, due to the forces created by the involution of thebraided tube (FIG. 16).

In another embodiment, the involution valve may be formed by a doublecylinder structure in which the innermost tube is folded inside theoutermost tube (FIG. 17). In the previous discussion of the presentinvention, the outermost tube is folded inside itself. In thisconfiguration, there can exist an additional cuff of tissue or scaffoldat one or both ends of the valve construct. An additional cuff at thebase of the valve would ease the surgical implantation of the valve bydecreasing the risk of distorting the leaflets during suture placementsince the leaflet are a distant from the sewing area at the cuff. Theadditional cuff(s) may be particularly useful for implantation of apulmonic valve replacement and reconstruction of the right ventricularoutflow tract.

Attachment

One exemplary method of attachment of the inner wall (with or withoutflaps) to the outer wall is by using three or more “U” sutures (FIG. 13,referred to previously). Other techniques of attaching the inner to theouter wall of the valve include, but are not limited to, interlacing,interlocking, stapling, clipping, splicing, suturing, screwing,knitting, braiding, weaving, punching, tufting (see FIG. 18), stapling,gluing, welding, fusing, laminating and combinations thereof and thelike.

Historically, tissue valves with leaflets secured by sutures failed dueto the stress imposed at the sites of attachment. In the design of thepresent invention, the tissue has retained or imparted with healingcapabilities that would theoretically offer reinforcement by enablingtissue growth and reinforcement at the suture sites.

A mathematical stress analysis of the involution valve constructed ofhuman blood vessel, indicated that an area of high stress would occur ina discrete area at each commissure (attachment area of the innerleaflets to the outermost wall) (see FIG. 19). In a dynamic model of thetheoretical involution valve structure during the cardiac cycle, thisarea of high stress was noted to move its position along the wall duringvarious phases of the cycle. In order to provide strength and dissipatethis small area of high stress, an involution valve can be created withan area of attachment between the leaflets and outer wall as opposed toa line or point of attachment. As a more specific example, an involutionvalve can be constructed by weaving, knitting, or braiding theinvolution and attachment areas of the inner leaflets and outermost wallof the valve.

Interleaflet Triangles

Native human semilunar valves have structures referred to asinterleaflet triangles. These structures represent a triangular regionbetween leaflets created by the angled attachment of the each leaflet tothe wall. In the present invention, an analogous structure can beimposed in the involution valve by creating a triangular area ofattachment of the leaflets to wall of the valve construct. This can becreated by interlocking or interlacing the material with weaving,braiding or knitting techniques (FIG. 20).

In the native human semilunar valves the annulus (imaginary coronalcircle representing the base of the valve) moves in opposition to thesinotubular junction (imaginary circle at the level of the leaflets mostsuperior attachment to the wall or sinus) during the cardiac cycle.During diastole, the annulus increases diameter as the sinotubularjunction decreases diameter. During systole, the reverse is true,namely, the annulus reduces diameter and the sinotubular junctionincreases diameter. This motion may be important for valve longevity andthe sharing of stress between the leaflet and wall during the cycle.Inserting interleaflet triangles into the involution valve construct mayhelp restore the opposing movement of the annulus with respect to thesinotubular junction. The alteration to the base of the valve constructto construct interleaflet triangles may permit independent movement ofleaflets in relationship to one another.

In certain instances, the present invention is created from a tissuecylinder, in this case the interleaflet triangle can be re-approximatedwith a linear angle of sutures to relieve the point stress at theleaflet commissures. Angling of the base of each leaflet more closelyapproximates the normal anatomy and helps disperse the stress on theleaflet to a tapered row of sutures rather than a single point ofattachment at each commissure.

Sinuses

In a human's native semilunar valve apparatus there exists a spacebetween each leaflet and the vessel wall referred to as the Sinus ofValsalva. This space is known to increase the efficiency of valvefunction by providing an eddy current of circulating blood whichfunctions, in part, to maintain the separation of the leaflet from thewall during the opening of the valve.

In the present invention, the outermost wall of the involuted cylindervalve construct can be purposefully enlarged at the base of the valve torecreate a potential space between the leaflet free edge and the outerwall. One exemplary method of creating the enlargement is to constructthe valve such that the outermost wall is a larger diameter than theinnermost wall cylinder. If the starting material is a tube, one way toachieve this is to use a conical shape of the material such that thesmaller diameter of the cone will be involuted into the larger diameterof the cone.

In more complicated methods of forming an involution valve, such asweaving, the sinuses can be integrated into the final geometry bycreating selective pockets or outpouchings in the outer wall (see FIG.21). Various techniques of weaving, knitting, and braiding can formpouches, pockets, pleats, corrugations, crimps and sinuses.Alternatively, portions of the outermost wall of the valve construct canbe removed by incisions or scalloping to preserve a potential space (thenative Sinus of Valsalva) to exist between the leaflet and the nativeaortic wall (FIG. 21).

Leaflet Modifications

As described previously, the native human semilunar valve leafletventricularis layer has gross corrugations of collagen and elastin inthe radial direction which impart significant compliance in thisorientation. In the circumferential direction, the fibrosa layer has acrimping of collagen that provides a counterforce to overextension ofthe leaflet during the period of more extreme loading-bearing(diastole). In order to more closely model the physical properties ofthe native human valve, the involution valve of the present inventionmay be constructed with excess material in the leaflet in the radialdirection or circumferential directions. (FIG. 22). The techniques offabricating the involution valve using knitting, weaving, or braiding ofmaterial are particularly useful, since excess material to create a“baggy” leaflet can be imparted during the sleeving process.Alternatively, excess material or pouches could be pleated during valveconstruction, particularly if the involution required folding ofmaterial. Using similar techniques, the leaflets of the involution valvecan have excess material in the longitudinal direction (FIG. 23).

Modifications of the leaflets' shape by sculpturing the free edge maymaximize leaflet coaptation (i.e., the adaptation or adjustment of partsto each other). Such alternative shape of leaflets include scalloping orrounding off the edges (concave). Other potential leaflet shapes areconvex or bi-convex with formation of a central nodule by purposefullyimparting a node shape at the midpoint. In certain cases, these shapesmay better mimic native valve anatomy and help valve function.

Stents

A sheet of woven, knitted, or braided material may be used incombination with a rigid or semi-rigid frame (“stent”) to create avalve. The stent can function to hold the valve in the involutedposition, which aids the surgeon in implantation. In another embodiment,a sheet of woven porcine (or other suitable source) decellularized smallintestinal submucosa is suspended in a stent (FIG. 24).

Implantation

If the involuted cylinder valve formed by any of the aforementionedmethods and materials is orientated such that following implantation,the most viable and anti-thrombogenic surface opposes the diastolic side(FIG. 1). The reason for this is that the highest mechanical stresses onthe leaflets and greatest degenerative changes in tissues valves havebeen noted on the diastolic surface (i.e., the inflow surface). In theinvolution valve construct (if derived from a blood vessel), theendothelium is orientated towards the diastolic side since it since itmay receive nutrients directly from the lumenal blood flow and mostlikely retains cellular repair capabilities.

As shown in FIG. 14 a design is provided for subcoronary implantationwhere the outer wall of the tissue cylinder is reduced between the threesuture points to permit implantation below the coronary arteries whenimplanted into the aortic position.

As shown in FIG. 25 the outer wall of tissue cylinder can remain intactand cut out for coronary artery re-implantation, inclusion or mini-rootimplantation.

One advantage of a tubular braid configuration is the possibility ofcreating a tubular valve that is collapsible (FIG. 26). Braided tubescan be constructed which reduce diameter significantly when alongitudinal force is exerted on the tube. For example in one exemplaryembodiment, the tubular valve is reduced in diameter by exerting alongitudinal force by a trocar on the inside of the tube, introducedinto the endovascular space in minimally invasive manner, and isdeployed as a larger diameter structure at the valve replacement site byremoving the trocar.

Apparatus and methods for forming, inserting and using expandable andcollapsible structures, e.g., cannulae, which may serve as an analogoustechnology useful for creating a scaffold capable of having a reduceddiameter during implantation and expanding thereafter are disclosed incopending Patent Cooperation Treaty (designating the U.S.) applicationNo. PCT/US02/40349, filed Dec. 16, 2002, entitled “DYNAMIC CANNULA”.

Alternative Scaffolding Techniques

A mold of scaffold can be created by a tricuspid “ventricular” and“aortic” stamp (e.g., a silicone-coated aluminum mold). Thermoplasticscaffolding material is inserted between the two stamps to create thecomplex shape of the aortic root and valve.

Some scaffold materials (such as, but not limited to, P4HB) withthermoplastic properties can be welded instead of sutured at thecommissures.

Computer-aided molecular deposition of scaffold material potentially beused in lithography to create the three-dimensional valve. The sameprocess could generate a flat sheet, cylinder, or cylinder with threeequidistant incisions (see the involuted cylinder method) which thenundergo secondary folding to create a valve.

Special Processes

The present invention also contemplates the construction of a scaffoldgenerally having the configuration made of a synthetic material, whichis then used as a support on which to seed and grow cells. The basicconcept of seeding is to transplant autologous cells onto abiocompatible and biodegradable scaffold that has been pre-formed in thethree dimensional structure of a heart valve. The cells are attached tothe scaffold while keeping tissues in vitro with physical signals toguide development of tissues. As the cells form extracellular matrix,the biodegradable polymer scaffold starts to degrade. The scaffold andthe attached cells are implanted into the body where cells continue toproduce matrix materials, providing increasing mechanical strength whilethe scaffold finishes its degradation (usually in about 6-8 weeks).

Possible culture additives include, but are not limited to, cytokines,growth factors, microencapsulated growth factors, heparin products, cellmarkers to track cells post-implantation, transfection vectors (e.g.,green fluorescent protein), anti-microbial anti-fungal agents, mixturesthereof and the like.

Possible cells which can be used to seed the scaffold include, but arenot limited to, fibroblasts, endothelial cells, myofibroblasts, smoothmuscle cells, fetal-type smooth muscle cells, mixtures thereof and thelike.

Cell sources include, but are not limited to, peripheral blood, humanumbilical cord, blood, arteries (e.g., carotid), human foreskin, bonemarrow, adipose tissue, mixtures thereof and the like.

Advantages

The involution valve can be constructed from a wide range of materials.The use of scaffolding materials (e.g., porcine small intestinal mucosa)offer the advantage of a potentially autologous living valve capable ofgrowth and repair following maturation of the implant in thecirculation.

The involution valve can being constructed as a braid, a knit, or aweave of material. The ability to fabricate the valve using thesetechniques enables the potential to create a valve with physicalproperties analogous to the native human leaflet. These techniquesincrease the potential strength and durability of the valve thereinforcement provided by interlacing the material at the attachmentareas of the leaflet to the wall. It is advantageous that the involutionvalve can be constructed as a continuous structure using thesetechniques.

In contrast to previous attempts to reconstruct autologous arteries intovalvular structures, the method described in this present inventionenables a tri-leaflet valve to be constructed independent from its siteof implantation. The valve may be transplanted to any desirableanatomical implant site. This reduces the technical challenge and allowsthe potential for pre-operative or intra-operative dynamic functiontesting prior to implantation. In certain instances, it is advantageousthat the involution valve can assume a narrow profile and be deployedinto the endovascular space by a minimally invasive means.

The involution valve can also be constructed from the patient's owntissues in an economical manner, offering an alternative treatment forvalvular disease. If the valve retains its growth potential, it may beparticularly useful for pulmonic valve substitution in the Rossprocedure or in pediatric patients with congenital abnormalities of thepulmonary valve such as tetralogy of Fallot with absent valve syndrome.

The invention may also have applicability to non-medical application.The advantage of this design and method is the potential to create avalve with the following properties; large effective orifice area, a lowpressure gradient, efficient closure velocity, and low regurgitationvolume. The valve is suitable in rigid or non-rigid systems and wet ordry environments. The valve leaflets can potentially form a seal aroundan inner rod or piston. The valve can be constructed from a wide rangeof materials. The valve is potentially efficient and economical toconstruct and insert into the stream of flow. The invention will befurther described in connection with the following examples, which areset forth for purposes of illustration only. Parts and percentagesappearing in such examples are by weight unless otherwise stipulated.

EXAMPLES Example 1

A tri-leaflet tissue valve can be constructed from the main pulmonaryartery by the involution method and implanted into the aortic positionin sheep (see experiment 1). This valve may also be suitable as areplacement for other valves (e.g., pulmonary valve).

Objective

An involuted cylinder valve constructed from pulmonary artery tissue andimplanted in the aortic position in sheep.

Materials and Methods

From previously sacrificed donor swine (n=4, 50 kg+/−10 kg), the mainpulmonary artery and its main left and right branches were harvested.The main pulmonary artery trunk was trimmed to create a tissue cylinderof height equal to the diameter of the recipient aortic annulus. A=h≈d,where A=recipient aortic annulus diameter (mm), h=tissue cylinder height(mm), and d=tissue cylinder diameter (mm). Excess fat was trimmed fromthe specimen and adventitial layer was carefully peeled off as a singlesheet of tissue and discarded. The tissue cylinder was incised with treelongitudinal incisions 120 degrees apart. L=½ h−2 t, where L=incisionlength (mm), and t=wall thickness (mm) (see FIG. 1).

In two specimens, the edges of all three flaps of tissues wererounded-off along their free-edge, creating concave-shaped leaflets. Inall constructs the flaps were involuted into the tissue cylinder andsutured to the cylinder wall at three equidistant points using “U”sutures (see FIGS. 2 and 3.). The outer wall of the valve construct wasreduced between the three points to allow space for implantation of thevalve inferior to the coronary arteries (see FIG. 4). In all cases, thevalve was prepared in less than 20 minutes. Prior to implantation, thevalve was inspected for competency by passive suspension of a column ofsaline.

A median sternotomy was performed and cardiopulmonary bypass wasinstituted in recipient sheep. Cold high potassium crystalloidcardioplegia was given by direct ostial cannulation. The ascending aortawas transversely transected 1 cm above the right coronary artery andnative leaflets excised. The preformed valve construct was secured intothe subcoronary position by interrupted 3-0 Tevdek™ sutures on the loweredge and a running 4-0 prolene along the superior aspect. The aortotomywas closed and the animal weaned from cardiopulmonary bypass. In animalsthat recovered cardiac function, echocardiography was performed toassess valve function.

Results

The two animals that received valve constructs without rounded-offleaflet free-edges displayed mild aortic regurgitation ontwo-dimensional echocardiography with continuous-wave Doppler using ahand-held epicardial probe. In the same group, the short-axis viewexhibited coaptation of all three leaflets during valve closure.Symmetrical leaflet movement and good mobility was observed throughoutthe cardiac cycle in four-chamber apical view. A mean flow velocity of2.49 m/sec was obtained in one animal with a 14 mm aortic annulusdiameter. The two animals with rounded-off leaflet free edges had severeaortic insufficiency due to prolapse of two or all three leaflets andcould not be weaned from bypass.

Conclusion

In this experiment, a segment of the main pulmonary artery wasreconfigured into an aortic valve using a technique referred to as the“involuted cylinder” method and implanted into the subcoronary positionin four sheep. In two constructs the leaflets were modified, creatingconcave leaflet free-edges. The modification was designed to eliminatedeadspace at the base of the leaflets and reduce the risk of thrombosisformation. However, in these modified constructs the central region ofthe leaflets was not supported adequately which resulted in leafletprolapse under diastolic load. The constructs without rounded leafletsassumed a more cup-like configuration and exhibited no prolapse, mostlikely due to the suspension of the leaflets at all points along thefree-edge. It may also be significant that the longitudinal axis of thepulmonary artery wall becomes the radial axis of the valve leaflet.Increased extensibility of the leaflet in the radial direction may actto lessen the central orifice by providing more coaptation area

Example 2

A scaffold is constructed of decellularized porcine small intestinalsubmucosa. The involution method described above is used to form afunctional three-dimensional valve. The valve is implanted into theindividual and allowed to mature under in vivo conditions.

Objective

A Pulmonic Valve Replacement in Sheep Using an Involution ValveConstructed of Porcine Small Intestinal Submucosa

Materials and Methods

A sheet of 4-ply porcine small intestinal submucosa “SIS” (Cook, Inc.)of dimensions 68.2 mm long×20 mm wide was prepared. Two equidistant 8 mmlong incisions were created extending from the free edge of the lengthto centerline of the material. The flat sheet was folded in half alongthe length with the smoother surface on the inside. A cylinder wasformed by suturing the two free ends together with a running 7-0prolene. The leaflets were secured in a perpendicular manner to theinner wall of the cylinder by “U” sutures. Two additional sheets of SISwere sutured to either end of the valve, creating two cylindrical cuffsof tissues at either end of the valve construct.

A median sternotomy was performed and cardiopulmonary bypass wasinstituted in a recipient sheep. Cold high potassium crystalloidcardioplegia was given by ascending aortic cannulation. The pulmonaryartery was clamped and transected one millimeter above the pulmonaryvalve. The native pulmonary valve was excised. The preformed valveconstruct was secured at the superior aspect to the distal pulmonarytrunk using 5-0 prolene. The cuff at the base of the valve was suturedto the proximal remnant of the pulmonary trunk Protomine™ was given andthe animal was weaned from cardiopulmonary bypass. The animal recoveredcardiac function and echocardiography was performed to assess valvefunction.

Results

The animal was successfully weaned from bypass. The pulmonary valvereplacement displayed no pulmonic regurgitation on two-dimensionalechocardiography with continuous-wave Doppler using a hand-heldepicardial probe. The short-axis view exhibited coaptation of all threeleaflets during valve closure. Symmetrical leaflet movement and goodmobility was observed throughout the cardiac cycle in four-chamberapical view.

Conclusion

An involution valve constructed from decellularized porcine smallintestinal submucosa functioned as a trileaflet pulmonary arteryreplacement in an acute sheep model. Chronic studies are necessary todetermine the ability of the scaffold material to endothelialize andpopulate with autologous cells following endovascular implantation.Further investigation as to the function of the valve followingimplantation will help determine its usefulness in patients.

Example 3

A sheet of the patient's pericardium is harvested and formed into avalve construct using the involution method as described hereinabove atthe surgical backtable. The valve construct is tested, then reimplantedinto the same patient as a living autologous valve replacement.

Example 4

Formation of Scaffold

An unwoven polyglycolic acid (“PGA”) mesh sheet 24 mm×75 mm and 1.5 mmthick is prepared and rolled into a cylinder. Three equidistantlongitudinal 10 mm incisions are used to create three flaps which areinvoluted inside the cylinder and secured 120 degrees apart to formcommissures. Scallop-shaped segments of the outermost wall of thecylinder are removed between the commissures to form the scaffold.

Example 5

Seeding

The scaffold of Example 4 created of a material that will supportcellular growth, e.g., celluloid. Peripheral blood is harvested, samplesare spun in column and cells are recovered (e.g., circulatingendothelial cells) which are then serial plated on fibronectin cultureplates and allowed to expand (e.g., static growth for 1 week). Cells arethen seeded onto a celluloid construct in a rotating, pulsatile, orcontinuous flow bioreactor for a period of time (e.g., 4 weeks), thenthe valve is implanted in the patient to continue to mature,differentiate, and evolve in vivo.

Example 6

A valve is created by any of the examples or methods discussedhereinabove and temporarily implanted in the body (endovascular or othersite) to allow maturation. For instance, the valve can be deployed usinga minimally invasive apparatus into the descending aorta, exposed to theblood stream and mechanical stresses of the cardiac cycle for a periodof weeks, and then removed from the body and reimplanted as a permanentvalve replacement.

Example 7

A valve is created by any of the examples or methods discussedhereinabove and implanted in the endovascular space using a minimallyinvasive means.

It will be understood that the terms “a” and “an” as used herein are notintended to mean only “one,” but may also mean a number greater than“one.” All patents, applications and publications referred to herein arehereby incorporated by reference in their entirety. While the inventionhas been described in connection with certain embodiments, it is notintended to limit the scope of the invention to the particular forms setforth, but, on the contrary, it is intended to cover such alternatives,modifications, and equivalents as may be included within the true spiritand scope of the invention as defined by the appended claims.

1. A method of forming a prosthetic valve, comprising: a. providing atube of material having an inner wall, an outer wall, a diameter “d”, aheight “h” and a wall thickness “t”; b. cutting three longitudinalincisions from one end in said material about 120 degrees apart to formthree flaps, each said flap having a first edge, a second edge generallyparallel to said first edge, and a bottom edge; c. involuting each saidflap within said tube; and, d. attaching each said first edge and secondedge of each involuted flap to said inner wall of said tube.
 2. Themethod of claim 1, wherein said three longitudinal incisions have alength “L”, such that L=½h−2t, where “h” is the tube height and “t” isthe thickness of said tube.
 3. The method of claim 1, wherein saidheight “h” is approximately equal to a diameter of a recipient aorticannulus diameter “A”.
 4. The method of claim 1, wherein the first,bottom, or second edges, or any combination therefore, of each flap arecut to be rounded off to create concave shaped leaflets.
 5. The methodof claim 1, wherein scallop shaped segments of said outer tube wall areremoved between commissures.
 6. The method of claim 1, wherein saidattaching is achieved by any one or more of suturing, interlacing,interlocking, stapling, clipping, splicing, screwing, knitting,braiding, weaving, punching, tufting, gluing, welding, fusing, andlaminating.
 7. The method of claim 1, wherein said tube is comprises agenerally rectangular sheet of material that has two opposing sidesjoined together.
 8. An endovascular valve, comprising: a. a flexibletube of material comprising a first end and a second end, an inner wall,and an outer wall; and b. a plurality of leaflets formed from a portionof said first end by making a plurality of longitudinal incisions insaid second end to form a plurality of flaps, each flap having a firstedge and second edge, involuting said flaps toward said inner wall andsecuring said first edge and second edge of each flap to said inner wallof said tube.
 9. The method of claim 1, wherein said attaching isachieved by any one or more of suturing, stapling, and gluing.
 10. Themethod of claim 1, wherein said attaching is achieved by suturing. 11.The valve of claim 8, wherein the material comprises a syntheticmaterial.
 12. The valve of claim 8, wherein the material comprises oneor more of a polyglycolic acid, a polyhydroxyalkanote, a polylacticacid, a polycaprolactone, a fibrin gel, poly-4-hydroxybutyrate, ahydrogel, a polyester, a metal, and a nitinol.
 13. The valve of claim11, wherein the material comprises one or more of polyglycolic acid,polylactic acid, and poly-4-hydroxybutyrate.
 14. The valve of claim 8,wherein the material comprises an organic material.
 15. The valve ofclaim 14, wherein the organic material comprises one or more of apolypropylene, a polyester, a silk, a nylon, a rubber, a silicone, acellulosic material, a polytetrafluoroethylene, and a polyurethane. 16.The valve of claim 14, wherein the organic material comprises one ormore of a polypropylene, a nylon, a silicone, and a polyurethane. 17.The valve of claim 8, wherein the material comprises a biologicalmaterial.
 18. The valve of claim 17, wherein the biological materialcomprises one or more of a pericardial tissue, an artery, a vein, aportion of a gastrointestinal tract, and a portion of an intestinalsubmucosa.
 19. The valve of claim 17, wherein the biological tissuecomprises one or more of an artery or a vein.
 20. The valve of claim 17,wherein the biological material is decellularized.
 21. The valve ofclaim 17, wherein the biological material comprises porcine tissue. 22.The valve of claim 17, wherein the biological material comprises humantissue.